Triazole antifungals. II. Synthesis and antifungal activities of 3-acyl-4-methyloxazolidine derivatives.
Triazole compounds with an oxazolidine ring were designed and synthesized as a potential inhibitor of the fungal cytochrome P450 14 alpha-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (4R,5R)-3-acyl-4-methyloxazolidine derivatives 4 exhibited remarkably high efficacy after oral or parenteral dosing. The potent activity of 4 is hypothesized to be a consequence of a structural similarity between 4 and lanosterol, a target molecule of the cytochrome P450 14 alpha-demethylase. Highly stereoselective synthesis of these oxazolidines is also described.
Konosu
T
T
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Tajima
Y
Y
Takeda
N
N
Miyaoka
T
T
Kasahara
M
M
Yasuda
H
H
Oida
S
S
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000138:chemical synthesis / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000935:Antifungal Agents; D010080:Oxazoles; D014230:Triazoles